Waterborne schistosome parasites are spreading in Africa and China and recently are appearing also in Europe. Rising water temperatures and altered precipitation associated with climate changes can considerably alter the distribution and abundance of the parasite intermediate host, a snail, resulting in a shift in disease dynamics and transmission to people, as already observed in Corsica (FR) where several tourists were infected by the parasite in 2014. Schistosomes infect 200 million people, resulting in significant morbidity and more than 200,000 deaths annually. Female genital schistosomiasis is a common complication of S. haematobium infections, occurring in approximately half of infected females, roughly 40 million girls and women, making it one of the most common gynecologic conditions in Africa. Schistosomiasis control strategies rely almost exclusively on praziquantel, administered to 40 millions people every year, with no new drugs in the clinical pipeline. We identified a highly promising drug target: the worm selenocysteine-containing enzyme thioredoxin glutathione reductase (TGR). We established that TGR is a central and essential mediator of antioxidant defenses in the worm. Our studies have elucidated an inhibitory mechanism that is completely novel for this family of proteins. We hypothesize that it will be possible to optimize our novel TGR inhibitors for potency for TGR inhibition for the development of novel schistosomicidal therapeutics.

Suggested skills:- heterologous expression of protein and their purification- biocrystallography- enzymology- protein-ligand binding

At present there are 1 assistant professor, one technician, 1 Ph.D student and 3 master students, which assure a young and active scientific environment in the lab.The group of Prof. Angelucci is well-equipped with all the technologies and instrumentations for structural and functional studies of protein and is already involved in a structural genomics project on Schistosoma mansoni. We have monthly scheduled synchrotron time to collect X-ray high resolution data on protein crystals; we are also participating in a national consortium of universities to get access to cryo-electron microscopy (Cryo-EM) facilities present in Europe.